Single and multiple administration of a new triphasic oral contraceptive to women: pharmacokinetics of ethinyl estradiol and free and total testosterone levels in serum

Ethinyl estradiol is part of almost every combined oral contraceptive, and its pharmacokinetic characteristics have been thoroughly investigated in numerous studies. However, little is known about its pharmacokinetics during long-term administration, as compared with single-dose administration. In this study 10 women received a triphasic formulation that contained ethinyl estradiol together with the progestin gestodene over one treatment cycle. Mean area under the curve values of ethinyl estradiol were significantly higher on the last treatment day, as compared with the corresponding values obtained from the same women after single-dose administration. However, the observed increase in area under the curve was within the range of pharmacokinetic accumulation, to be expected on the basis of dosing interval and terminal half-life. Another point of interest was the effect of the triphasic preparation on testosterone concentrations in serum. Both total and free testosterone levels were suppressed by about 60% as compared with pretreatment values, and there was no correlation with corresponding sex hormone-binding globulin levels in the serum.